It is the purpose of this study to investigate at a mechanical, hemodynamic and subcellular level the defects in myocardial function that may be responsible for the cardiovascular failure observed in gram negative endotoxin and septic shock. Three canine models of shock will be developed: a five hour endotoxin shock model, an eight hour E. coli septic shock model and a chronic septic shock model. The first objective of this study will be the characterization of endotoxin and septic shock on myocardial function. This will be documented on three levels: 1) Hemodynamic (systemic and pulmonary arterial pressure, cardiac output, LV pressure, coronary flow and calculated pulmonary, systemic and coronary vascular resistance); 2) Mechanical (dP/dt-max, +dP/dt, -dP/dt and isovolumetric LV pressure before and after catecholamine stimulation); 3) Subcellular level (sarcoplasmic reticulum calcium uptake, binding and ATPase activity and myofibrillar calcium sensitivity, binding and ATPase activity). The second objective of this study will concentrate on interrupting the circle of positive feedback of decreasing cardiac output, increasing peripheral and coronary vascular resistance and decreasing coronary flow. LV filling pressure will be optimized by volume expansion. LV afterload will be reduced either mechanically, utilizing an A-V shunt, or pharmacologically with sodium nitroprusside. It is hypothesized that by optimizing preload and reducing afterload, cardiac output, coronary flow, and myocardial mechanical and subcellular function should be preserved.